This project uses Image Processing techniques to analyze electron micrographs. In order to answer important questions in structural biology, it is necessary to obtain relatively high resolution two- and three-dimensional structural information about biological macromolecules. While atomic or near atomic resolution information has traditionally been available by x-ray crystallography for some small molecules and small proteins, the overwhelming majority of biological macromolecules are not crystalline, or are too large and therefore not amenable to 3-D crystallography. Biological specimens can, on the other hand, be visualized in the electron microscope using a number of specimen preparation techniques. Cryo- electron microscopy, for example, attempts to preserve 'native' structure by surrounding the specimen in a layer of ice. Collaborative research with LSBR, NIAMS is currently underway on a number of projects whereby the e.m. images are computationally corrected, combined, average, reconstructed, or in some way computationally enhanced in order to improve the signal-to- noise ratio or increase the interpretability of the structures being visualized.